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The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtraction radiography, serum and plaque biofilm assessments. Saliva and serum were analyzed with protein arrays for 14 pro-inflammatory and bone turnover markers, while qPCR was used for detection of biofilm. A hierarchical clustering algorithm was used to group study participants based on clinical, microbiological, salivary/serum biomarkers, and PDP. Eighty-three individuals completed the six-month monitoring phase, with 39 [corrected] exhibiting PDP, while 44 [corrected] demonstrated stability. Participants assembled into three clusters based on periodontal pathogens, serum and salivary biomarkers. Cluster 1 members displayed high salivary biomarkers and biofilm; 71% [corrected] of these individuals were undergoing PDP. Cluster 2 members displayed low biofilm and biomarker levels; 76% [corrected] of these individuals were stable. Cluster 3 members were not discriminated by PDP status; however, cluster stratification followed groups 1 and 2 based on thresholds of salivary biomarkers and biofilm pathogens. The association of cluster membership to PDP was highly significant (p < 0.0007). [corrected] The use of salivary and biofilm biomarkers offers potential for the identification of PDP or stability (ClinicalTrials.gov number, CT00277745).

Background: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm., Methods: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers., Results: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5)., Conclusions: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

Background: Along with conventional surgical therapy, systemic antibiotics may provide more effective treatment in smokers by targeting tissue-invasive bacteria. The aim of this randomized, placebo-controlled, double-masked clinical trial was to evaluate the adjunctive effects of systemic azithromycin (AZM) in combination with periodontal pocket reduction surgery in the treatment of chronic periodontitis in smokers., Methods: Thirty patients with a greater than one pack/day smoking habit and generalized moderate to severe chronic periodontitis were randomized to the test (surgery plus 3 days of AZM, 500 mg) or control group (surgery plus 3 days of placebo). Full-mouth probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), plaque index, and wound healing indices (WHI) were assessed at baseline and at 2 weeks and 1, 3, and 6 months following surgical intervention. Plaque and gingival crevicular fluid were collected for trypsin-like enzyme activity (benzoyl-dl-arginine naphthylamine) and bone biomarker (crosslinked telopeptide of type I collagen [ICTP]) analyses, respectively, at baseline, 2 weeks, and 1, 3, and 6 months., Results: Surgical treatment of moderate (PD = 4 to 6 mm) and deep (PD > 6 mm) pockets significantly improved clinical parameters of treated and untreated teeth (CAL gain, PD reduction, and reduction of BOP). The additional use of AZM did not enhance this improvement nor did it promote reduction of ICTP levels. Compared to the control group, the test group had significantly better WHI scores at 1 month, significantly less GI at 2 weeks, and sustained reductions of red-complex bacteria with trypsin-like enzyme activity at 3 months. For non-surgery teeth, only the test group showed significant gains in overall CAL compared to baseline., Conclusions: The findings of this pilot study demonstrated that in heavy smokers, adjunctive systemic AZM in combination with pocket reduction surgery did not significantly enhance PD reduction or CAL gain. However, the clinical value of adjunctive AZM may be appreciated by more rapid wound healing, less short-term gingival inflammation, and sustained reductions of periopathogenic bacteria. More expanded studies are recommended to better determine the clinical effects of adjunctive AZM in patients who smoke.

Objective: To determine the prevalence and impact of mandated preterm deliveries at a tertiary referral center., Methods: A chart review was conducted at our institution on all livebirths from 24 weeks to completion of 37 weeks' gestation between 1 January 1998 and 31 December 1999. Mandated delivery was defined as intentional intervention because of a deteriorating maternal or fetal condition. Reasons for intervention and intrapartum courses were compared with two other preterm groups (premature ruptured membranes, spontaneous labor) delivering during the same period. Statistical analyses included the Student t test, univariate ANOVA, X2 test and Mann-Whitney test., Results: A total of 894 pregnancies delivered preterm, with 132 (14.8%) being mandated. Primary reasons for mandated delivery included severe pre-eclampsia (69.0%), vaginal bleeding (11.4%), deteriorating maternal illness (10.6%), worsening fetal growth restriction (6.1%) or major fetal malformation (3.0%). Delivery at less than 34 weeks was more common in the mandated group (68.9%) than in the ruptured membranes group (41.2%, p < 0.005) or in the spontaneous labor group (46.5%; p < 0.01). Cesarean section rates were higher in the mandated group (69.7%) than in the ruptured membranes group (18.3%; p <0.001) or in the spontaneous labor group (21.5%; p < 0.001). The presence of an unfavorable cervix, unsuccessful trial of labor, non-cephalic fetal presentation, or fetal intolerance of labor explained the high rate of surgery., Conclusions: Conditions mandating delivery accounted for 14.8% of all preterm births. Mandated delivery is associated with a greater need for delivery before 34 weeks, often by Cesarean section.

Objective: To compare the rates of and indications for labor induction between a university hospital and two community hospitals and to examine the risk of cesarean delivery among labor induction cases., Study Design: Labor induction cases over a six-month period were included (N = 536). Medical records were reviewed by a trained abstractor using a standardized form to determine maternal characteristics, reason for induction and perinatal outcomes., Results: Rates of labor induction were significantly different between the three hospitals: university, 18.2%; community hospital A, 21.4%; community hospital B, 33.7% (P < .001). At the university hospital, 95% of labor inductions were medically indicated using American College of Obstetricians and Gynecologists (ACOG) criteria. Forty-four percent of labor inductions at community hospital A and 57% at community hospital B were for elective reasons. Cesarean rates among induction cases were highest at the university hospital (19%) as compared to community hospital A (15%) and community hospital B (11%), although the difference was not statistically significant. Parity, race and cervical status, but not elective induction, were significantly associated with cesarean delivery., Conclusion: Labor induction was more frequent in community hospitals but more likely to meet ACOG-approved indications at the university hospital. The more-frequent inductions at the community hospitals did not result in higher cesarean rates.

In utero exposure to a single dose of the long-acting corticosteroid betamethasone at GD 14 has been shown to induce specific differences in motivation/anxiety testing among offspring. Because multidosings are desired to enhance fetal lung maturation, our objective was to compare effects of multidosings of betamethasone with a placebo on postnatal tests of motivation and anxiety. Sixty gravid CD-1 mice were randomly assigned to receive one of six treatment regimens (n = 10) that consisted of a single or a double SC dosing of either betamethasone (Celestone soluspan 0.2 mg on GD 14; 0.1 mg on GD 13 to 16; 0.1 mg b.i.d. on GD 14 and 15; 0.1 mg b.i.d. on GD 13 to 16) or saline (0.25 ml on GD 13 to 16; 0.25 ml b.i.d. on GD 13 to 16). The percent of pups exhibiting separation vocalization was temporarily less at PND 5 after betamethasone exposure to four doses (p < 0.05) and to eight doses (p < 0.01). The percents of pups being successful in homing (PND 9) and in responding to startle stimulation (PND 12-15) were not different between the betamethasone-exposed and placebo-exposed groups. Exploratory performance in the radial arm maze revealed no delay in the activities of juvenile and adult offspring exposed to betamethasone. The percent of male offspring that fought as juveniles and as adults was not different between the betamethasone-exposed and the placebo-exposed groups. The previously reported altered responses using the elevated plus maze, among juvenile and adult offspring, after a single dose of betamethasone was not replicated in this multidose study. These data indicate that prenatal exposure to betamethasone did not affect the mouse offspring's long-term responses to motivation/anxiety testing.